Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion
Authors: Pierre Bouzat, Jonathan Charbit, Paer-Selim Abback, Delphine Huet-Garrigue, Nathalie Delhaye, Marc Leone, Guillaume Marcotte, Jean-Stéphane David, Albrice Levrat, Karim Asehnoune, Julien Pottecher, Jacques Duranteau, Elie Courvalin, Anais Adolle, Dimitri Sourd, Jean-Luc Bosson, Bruno Riou, Tobias Gauss, Jean-François Payen, Jules Greze, Pierluigi Banco, Karine Berger, Stéphanie Druge, Martin Dupuis, Laure Janin, Caroline Machuron, Marine Thomas, Clotilde Schilte, Emmanuelle Hamad, Laurent Zieleskiewicz, Gary Duclos, Charlotte Arbelot, Karine Bezulier, Caroline Jeantrelle, Mathieu Raux, Pauline Glasman, Anatole Harrois, Virginie Tarazona, Aline Lambert, Olivia Vassal, Anne Li, Nicolas Grillot, Loïs Henry, Elise Blonde, Benjamin Bijok, Aurélien Rohn, Julie Bellet, Florence Lallemant, Nathalie Bruneau, Christine Ducam, Geoffrey Dagod, Pauline Deras, Xavier Capdevila, Magdalena Szczot, Alain Meyer, Stéphane Hecketsweiler, Etienne Escudier, Michel Muller, Samuel Gray, Magalie Farines, Marie Lebouc, Sophie DEBORD-PEDET
Journal: JAMA (2023)

Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption.To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion.Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021.Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines.The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety).Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03).Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion.ClinicalTrials.gov Identifier: NCT03218722.